全文获取类型
收费全文 | 4413篇 |
免费 | 373篇 |
国内免费 | 402篇 |
出版年
2024年 | 13篇 |
2023年 | 58篇 |
2022年 | 145篇 |
2021年 | 252篇 |
2020年 | 164篇 |
2019年 | 203篇 |
2018年 | 193篇 |
2017年 | 147篇 |
2016年 | 219篇 |
2015年 | 247篇 |
2014年 | 282篇 |
2013年 | 315篇 |
2012年 | 369篇 |
2011年 | 342篇 |
2010年 | 215篇 |
2009年 | 187篇 |
2008年 | 228篇 |
2007年 | 176篇 |
2006年 | 187篇 |
2005年 | 165篇 |
2004年 | 155篇 |
2003年 | 119篇 |
2002年 | 130篇 |
2001年 | 99篇 |
2000年 | 90篇 |
1999年 | 84篇 |
1998年 | 59篇 |
1997年 | 58篇 |
1996年 | 46篇 |
1995年 | 38篇 |
1994年 | 40篇 |
1993年 | 24篇 |
1992年 | 21篇 |
1991年 | 25篇 |
1990年 | 15篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 15篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有5188条查询结果,搜索用时 31 毫秒
91.
Liuhua Yan Qingzhe Zhai Jianing Wei Shuyu Li Bao Wang Tingting Huang Minmin Du Jiaqiang Sun Le Kang Chang-Bao Li Chuanyou Li 《PLoS genetics》2013,9(12)
In response to insect attack and mechanical wounding, plants activate the expression of genes involved in various defense-related processes. A fascinating feature of these inducible defenses is their occurrence both locally at the wounding site and systemically in undamaged leaves throughout the plant. Wound-inducible proteinase inhibitors (PIs) in tomato (Solanum lycopersicum) provide an attractive model to understand the signal transduction events leading from localized injury to the systemic expression of defense-related genes. Among the identified intercellular molecules in regulating systemic wound response of tomato are the peptide signal systemin and the oxylipin signal jasmonic acid (JA). The systemin/JA signaling pathway provides a unique opportunity to investigate, in a single experimental system, the mechanism by which peptide and oxylipin signals interact to coordinate plant systemic immunity. Here we describe the characterization of the tomato suppressor of prosystemin-mediated responses8 (spr8) mutant, which was isolated as a suppressor of (pro)systemin-mediated signaling. spr8 plants exhibit a series of JA-dependent immune deficiencies, including the inability to express wound-responsive genes, abnormal development of glandular trichomes, and severely compromised resistance to cotton bollworm (Helicoverpa armigera) and Botrytis cinerea. Map-based cloning studies demonstrate that the spr8 mutant phenotype results from a point mutation in the catalytic domain of TomLoxD, a chloroplast-localized lipoxygenase involved in JA biosynthesis. We present evidence that overexpression of TomLoxD leads to elevated wound-induced JA biosynthesis, increased expression of wound-responsive genes and, therefore, enhanced resistance to insect herbivory attack and necrotrophic pathogen infection. These results indicate that TomLoxD is involved in wound-induced JA biosynthesis and highlight the application potential of this gene for crop protection against insects and pathogens. 相似文献
92.
Xuan He Dan Li Zhenwu Luo Hua Liang Hong Peng Yangyang Zhao Nidan Wang Donghua Liu Chuan Qin Qiang Wei Huimin Yan Yiming Shao 《PloS one》2013,8(2)
Increasing evidence indicates that antibody-dependent cellular cytotoxicity (ADCC) contributes to the control of HIV/SIV infection. However, little is known about the ADCC function of natural killer (NK) cells in non-human primate model. Here we demonstrated that ADCC function of NK cells was significantly compromised in chronic SIV/SHIV infection, correlating closely with the expression of FcγRIIIa receptor (CD16) on NK cells. CD32, another class of IgG Fc receptors, was identified on NK cells with higher expression in the infected macaques and the blockade of CD32 impacted the ability of NK cells to respond to antibody-coated target cells. The inhibition of matrix metalloproteases (MMPs), a group of enzymes normally involved in tissue/receptor remodeling, could restore NK cell-mediated ADCC with increased CD16 expression on macaque NK cells. These data offer a clearer understanding of NK cell-mediated ADCC in rhesus macaques, which will allow us to evaluate the ADCC repertoire arising from preclinical vaccination studies in non-human primates and inform us in the future design of effective HIV vaccination strategies. 相似文献
93.
Shu Tang Rehana Buriro Zhijun Liu Miao Zhang Islam Ali Abdelnasir Adam J?rg Hartung Endong Bao 《PloS one》2013,8(7)
Neonatal rat primary myocardial cells were subjected to heat stress in vitro, as a model for investigating the distribution and expression of Hsp27 and αB-crystallin. After exposure to heat stress at 42°C for different durations, the activities of enzymes expressed during cell damage increased in the supernatant of the heat-stressed myocardial cells from 10 min, and the pathological lesions were characterized by karyopyknosis and acute degeneration. Thus, cell damage was induced at the onset of heat stress. Immunofluorescence analysis showed stronger positive signals for both Hsp27 and αB-crystallin from 10 min to 240 min of exposure compared to the control cells. According to the Western blotting results, during the 480 min of heat stress, no significant variation was found in Hsp27 and αB-crystallin expression; however, significant differences were found in the induction of their corresponding mRNAs. The expression of these small heat shock proteins (sHsps) was probably delayed or overtaxed due to the rapid consumption of sHsps in myocardial cells at the onset of heat stress. Our findings indicate that Hsp27 and αB-crystallin do play a role in the response of cardiac cells to heat stress, but the details of their function remain to be investigated. 相似文献
94.
Wei Bao Lei Jin Hai-jing Fu Yong-nian Shen Gui-xia Lu Huan Mei Xin-zhi Cao Hong-sheng Wang Wei-da Liu 《PloS one》2013,8(6)
Background
In recent years, the fungal infectious disease zygomycosis has increased in incidence worldwide, especially among the immunodeficient population. Despite the rates of zygomycosis-related death and deformation being very high, the mechanism(s) by which the fungal pathogens cause these severe manifestations remain unknown.Methods
Using the associated Rhizomucor variabilis species, which can selectively induce cutaneous zygomycosis in otherwise healthy individuals, we investigated the host mechanisms of infection-related responses, including cytokine and chemokine expression as well as contributions of particular T cell subsets. siRNA specifically targeting IL-22,IL-17 and IFN-γ were used to down-regulate expression of those molecules.Results
In mouse models of infection, IL-22 was implicated in development of Rhizomucor spp.-induced skin lesions. In cultured human peripheral blood monocytes, R. pusilluscan, which is often found in immunodeficient patients, induced the production of IL-22, while R. variabilis did not. Moreover, Rhizomucor spp.-induced secretion of Il-22 from CCR6+CCR4+CCR10+ cells was down-regulated by knockdown of IL-22 related signaling receptors, RORC and ARH.Conclusion
Our data strongly suggest that avoidance of IL-22 may be one mechanism by which mucor species produce morbidity and mortality in infected individuals. 相似文献95.
Mechanisms governing the metastasis of endometrial carcinoma (EC) are poorly defined. Recent data support a role for the cell surface receptor tyrosine kinase TrkB in the progression of several human tumors. Here we present evidence for a direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are more highly expressed in EC than in normal endometrium. High TrkB levels correlated with lymph node metastasis (p<0.05) and lymphovascular space involvement (p<0.05) in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the migratory and invasive capacity of cancer cell lines in vitro and resulted in anoikis in suspended cells. Conversely, exogenous expression of TrkB increased cell migration and invasion and promoted anoikis resistance in suspension culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in altered the expression of molecular mediators of the epithelial-to-mesenchymal transition (EMT). RNA interference (RNAi)-mediated depletion of the downstream regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial transition and anoikis in vivo. Our data support a novel function for TrkB in promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential therapeutic target in human EC. 相似文献
96.
Background
Elevated plasma levels of lipoprotein(a) (Lp(a)) and a higher degree of coronary artery calcification (CAC) are both considered to be risk factors for atherosclerosis. However, previous studies have demonstrated that the relationship between Lp(a) levels and the degree of CAC indicates significant heterogeneity that may be due to varying ethnicities. The purpose of this study was to examine the predictive power of Lp(a) for CAC as measured by multidetector computed tomography (MDCT) in the Han ethnic group of China.Methods
A total of 1082 subjects were recruited in this study. The patients were divided into four groups: patients without hypertension or diabetes were group 1, patients with hypertension were group 2, patients with diabetes were group 3 and patients with both hypertension and diabetes were group 4. CAC score (CACs), lipid profiles (Lp(a), LDL, HDL, TG, TC), HbA1C, glucose, personal health history and body morphology were measured in all participants. The predictive power of Lp(a) for calcified atherosclerotic plaque was determined by correlations and ordinal logistic regression.Results
There was no significant difference in the CACs between group 2 and group 3 (z = 1.790, p = 0.736), and there were significant differences among the other groups. However, there was no significant difference in the total Lp(a) among the 4 groups (χ2 = 0.649, p = 0.885). Only In group 1, Lp(a) was a statistically significant predictor of the presence of calcified coronary plaque using ordinal logistic regression.Conclusions
Levels of Lp(a) positively correlate with CACs among Chinese Han people who are without diabetes and hypertension, suggesting that Lp(a) may be an important risk factor for the presence of calcified atheromas. 相似文献97.
Objective
This study determined the prevalence and factors associated with peripheral neuropathy (PN) in subjects with diabetes mellitus, impaired glucose regulation (IGR), and normal glucose tolerance (NGT) in a community-based Chinese population.Research Design and Methods
A total of 2035 subjects in Shanghai were classified as having NGT, IGR, or diabetes. All subjects underwent complete foot examination. PN was assessed according to the neuropathy symptom and neuropathy disability scores. Binary logistic regression was performed to analyze the contributions of factors to PN.Results
The prevalence of PN was 8.4%, 2.8%, and 1.5% in diabetes mellitus, IGR, and NGT subjects, respectively (P<0.05 for diabetes vs. NGT, and IGR). The subjects with known diabetes had the highest frequency of PN (13.1%). Among the subjects without diabetes, those with PN were older, had a higher waist circumference and 2-h postprandial plasma glucose levels, and were more likely to be hypertensive. Among the IGR subjects, other than age, the 2-h postprandial plasma glucose level was an independent factor significantly associated with PN. Meanwhile, among the subjects with diabetes, PN was associated with fasting plasma glucose, duration of diabetes, and decreased estimated glomerular filtration rate.Conclusions
The prevalence of PN is slightly higher in individuals with IGR than that in individuals with NGT, but small fibre damage in IGR as the earliest nerve fibre deficit may be underestimated in our study. As an independent risk factor, postprandial plasma glucose level may be an important target for strategies to prevent or improve PN in IGR subjects. 相似文献98.
Yuki Ito Jose Luis Vela Fumiko Matsumura Hitomi Hoshino Aaron Tyznik Heeseob Lee Enrico Girardi Dirk M. Zajonc Robert Liddington Motohiro Kobayashi Xingfeng Bao Jeanna Bugaytsova Thomas Borén Rongsheng Jin Yinong Zong Peter H. Seeberger Jun Nakayama Mitchell Kronenberg Minoru Fukuda 《PloS one》2013,8(12)
Approximately 10–15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18−/−) or wild-type mice, bacterial recovery significantly increased in Jα18−/− compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18−/− compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis. 相似文献
99.
Wang Pei Wang Chun-Mei Gao Li Cui Yan-Nong Yang Hai-Li de Silva Nayana D. G. Ma Qing Bao Ai-Ke Flowers Timothy J. Rowland Owen Wang Suo-Min 《Plant and Soil》2020,448(1-2):603-620
Plant and Soil - Uncontrolled uptake of Na+ is the reason that many species are sensitive to salinity. Suberin is a protective barrier found in the walls of root endodermal cells that appears to be... 相似文献
100.
Plant Cell, Tissue and Organ Culture (PCTOC) - Tree peony (Paeonia sect. Moutan) is a world famous ornamental and economically important species, but it is recalcitrant to in vitro regeneration.... 相似文献